Editorial
Pheochromocytoma in Pregnancy
Kacy Church and Marina Basina*
Department of Endocrinology, Stanford University School of Medicine, USA
*Corresponding author: Marina Basina, Department of Endocrinology, Stanford University School of Medicine, USA
Published: 19 May, 2017
Cite this article as: Church K, Basina M.
Pheochromocytoma in Pregnancy. Clin
Surg. 2017; 2: 1474.
Editorial
Pheochromocytoma during pregnancy remains a rare condition, occurring in 0.007% in one 22-
year review of 30,426 pregnancies [1]. However, pheochromocytomas in pregnancy are associated
with high maternal and fetal mortality (8% and 17%, respectively) in addition to fetal growth
restriction and prematurity [2,3]. Antenatal diagnosis has been shown to reduce maternal and fetal
mortality with early pharmacologic and surgical intervention [4].
We present a case of a 29 year-old G2P1011 female was referred to endocrine clinic for elevated
plasma metanephrines that were checked in the setting of hypertension associated with headaches
and hyperhidrosis that persisted following a spontaneous abortion at 30 weeks gestation.
The patient had a history of gestational hypertension during her first pregnancy, but had not
routinely checked her blood pressure since her previous delivery 2 years prior. Early in her second
pregnancy she began to develop episodes of paroxysmal headaches, palpitations, and heat intolerance
associated with elevated blood pressure. She was diagnosed with gestational hypertension and
diabetes in the first trimester and placed on bed rest. Despite the start of labetalol in pregnancy,
she continued to have ongoing hypertension with episodic adrenergic symptoms. These symptoms
persisted after the pregnancy loss. She remained on labetalol therapy after the pregnancy.
Two months after abortion, labs showed elevated plasma free metanephrines to 4.6 nmol/L
(ref < 0.50), plasma free normetanephrines elevated to 35 nmol/L (ref < 0.90), 24 h metanephrines
6766 mg (ref 94-604), 24 h urine normetanephrines 5120 mg (ref 40-412). CT adrenal protocol
showed a 3.7 cm mass replacing the left adrenal with poor washout on delayed imaging. Labetalol
was discontinued and she was switched to phenoxybenzamine with left laparoscopic adrenalectomy
two months after initial laboratory diagnosis.
Pheochromocytoma is often misdiagnosed as pregnancy induced hypertension (PIH), which
remains the most common complication of pregnancy. However, there are some key differences
that can aid in distinguishing the two entities. PIH rarely occurs prior to 20 weeks gestation, while
symptomatic pheochromocytoma can present at any point during pregnancy. Pheochromocytoma
often presents with paroxysmal hypertension associated with headache, palpitations (40%),
hyperhidrosis (35%), and anxiety (18%) [5]. Idiopathic hypertension and PIH can often progress
to preeclampsia, which is associated with proteinuria, leg edema, and extra weight gain during
pregnancy. High uric acid, liver function abnormalities, and coagulopathies are more common in
PIH and hyperglycemia can be seen in either condition [6]. Cardiomyopathy during pregnancy or in
early post-partum should also raise the index of suspicion for pheochromocytoma [7]. One difficulty
in distinguishing the two entities is that both plasma and urine metanephrines and catecholamines
can be elevated in PIH, as much as 1.6 to 2.6 fold in one study [8]. However, other studies have
reported that catecholamines are not elevated in normotensive pregnant women or preeclamsia
[9]. It should be noted that some medications used in pregnancy (methyldopa, labetalol) can mildly
increase metanephrine levels. However, these elevations are not to the same degree as is seen in
pheochromocytoma. Plasma free metanephrines and 24 h urinary fractionated metanephrines
remain the screening tests of choice, with sensitivity close to 100% [10].
Both adrenal ultrasound and MRI can be used as diagnostic modalities for identifying adrenal
masses in pregnancy once biochemical testing has shown metanephrine excess. In one review,
adrenal ultrasound had a sensitivity of 54% and MRI had a sensitivity of 93% [3]. The sensitivity of
ultrasound declines in the third trimester with enlargement of the uterus.
The first step in management of pheochromocytoma in pregnancy is similar to that of nonpregnant
adults. Alpha blockade, typically with phenoxybenzamine 10 mg twice daily should be
started, with up-titration every 2-3 days to reach orthostatic blood pressures. Beta-blockade can
then be added to address reflex tachycardia that develops in the setting of orthostasis. If antenatal diagnosis is made prior to 24 weeks gestation, improved maternal and fetal outcomes have been shown with laproscopic adrenalectomy
between 12-24 weeks once adequate alpha blockade is achieved,
particularly if tumor is less than 7 cm. Bilateral pheochromocytoma
is not a contraindication to laparoscopic intervention. If diagnosis
made after 24 weeks, cesarean section should be performed at term
combined with tumor removal [11].
While pheochromocytoma in pregnancy remains rare, clinicians
should have a low threshold for testing in several clinical scenarios:
1) women with labile or difficult to control blood pressure early in
pregnancy 2) women with concurrent symptoms of paroxysmal
headaches, palpitations, and/or hyperhidrosis 3) women with
persistent symptoms after childbirth, or 4) finding of elevated blood
glucose early in pregnancy along with elevated blood pressure and
inability to gain weight as gestational age advances. No guidelines are
available due to the rarity of this condition but early recognition and
intervention are extremely important. Maternal and fetal outcomes
are markedly improved with early antenatal diagnosis and rates of
antenatal diagnosis have improved dramatically over the years with a
higher index of suspicion and improved biochemical testing.
References
- Harrington JL, Farley DR, van Heerden JA, Ramin KD. Adrenal tumors and pregnancy. World J Surg. 1999;23(2):182-6.
- Biggar MA, Lennard TW. Systematic review of phaeochromocytoma in pregnancy. Br J Surg. 2013;100(2):182-90.
- Sarathi V, Lila AR, Bandgar TR, Menon PS, Shah NS. Pheochromocytoma in pregnancy: a rare but dangerous combination. Endocr Pract. 2010;16(2):300-9.
- Lenders JW. Pheochromocytoma and pregnancy: a deceptive connection. Eur J Endocrinol. 2012;166(2):143-50.
- Pearson GAH, Eckford SD, Trinder J, Levy A. A reason to panic in pregnancy. Lancet. 2009;374:756.
- Perte A, Paragliola RM, Salvatori R, Coresello SM. Management of catecholamine-secreting tumors in pregnancy: a review. Endocr Pract. 2016;22(3):357-70.
- Kim HJ, Kim DK, Lee SC, Yang SH, Yang JH, Lee WR. Pheochromocytoma Complicated With Cardiomyopathy After Delivery: A Case Report and Literature Review. Korean J Intern Med. 1998;13(2):117-22.
- Zuspan FP. Catecholamines: Their role in pregnancy and the development of pregnancy-induced hypertension. J Reprod Med. 1979;23(3):143-50.
- Pedersen EB, Christensen NJ, Christensen P, Johannesen P, Kornerup HJ, Kristensen S, et al. Preeclampsia -a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia. Hypertension. 1983;5(1):105-11.
- Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. eochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-42.
- Lansdown A, Rees DA. Endocrine oncology in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011;25(6):911-26.